Support is sought for a broad and integrated program in epithelial and renal research. A wide range of approaches will be used to investigate the mechanisms of electrolyte and fluid transport across polarized cells, especially those of the nephron. The component projects will investigate the molecular transport operations (ion channels, pumps and coupled transport) mediating Na,K, C1 and H transport, using isolated tubules, renal and mesangial cell cultures, single tubule cells, renal membranes and transport proteins. The broad range of studies will include not only effort to identify the molecular structure of transport proteins but also to understand the mechanisms governing their distribution and insertion into epithelial membrane. The interaction between ion transporters and their regulations will also be studies. Several core facilities will support the strongly interactive research projects. These core units include one for developing and maintaining electronic equipment, and expanded unit for imaging techniques and a cell culture core facility. By providing novel information about the molecular and cellular mechanisms of ion and fluid transport, our studies also will improve the understanding and treatment of renal diseases and clinical electrolyte disorders. They also may provide a rational basis for developing new diuretics with fewer harmful side effects.